The present invention relates to a prostate-specific membrane antigen (PSMA)-specific binding protein, wherein the PSMA-specific binding protein is a lipocalin 2 (Lcn2)-derived binding protein and binds to PSMA with a K.sub.D of 10 nM or lower. The present invention also relates to a nucleic acid molecule encoding the PSMA-specific binding protein of the invention, a vector comprising said nucleic acid molecule of the invention and a host cell transformed with the vector. Furthermore, the invention relates to a method of producing the PSMA-specific binding protein of the invention, the method comprising culturing the host cell of the invention under suitable conditions and isolating the PSMA-specific binding protein produced. The present invention further relates to a protein conjugate comprising the PSMA-specific binding protein of the invention, or the PSMA-specific binding protein produced by the method of the invention. In addition, the present invention relates to a pharmaceutical or diagnostic composition; to the PSMA-specific binding protein of the invention, the nucleic acid molecule of the invention, the vector of the invention, the host cell of the invention or the PSMA-specific binding protein produced by the method of the invention, for use in therapy and/or diagnosis, and in particular for use in the therapy and/or diagnosis of tumors, Crohn's disease and/or neurological diseases.

The present invention relates to a method for preparing a fusion protein having an IgG Fc domain and, specifically, to a method for preparing a fusion protein having an IgG Fc domain, the method additionally comprising a step of culturing cells, which produce the fusion protein, at a decreased culture temperature, thereby increasing cell growth and cell viability so as to increase fusion protein productivity and inhibiting aggregate generation so as to improve quality and production yield.

The present disclosure relates to methods for producing recombinant proteins, as well as compositions used in and produced by such methods. Specifically, the present disclosure relates to methods for producing high secreted yields of recombinant proteins, and the compositions provided herein include recombinant host cells that comprise polynucleotide sequences encoding proteins operably linked to at least 2 distinct secretion signals.

The invention relates to methods of producing eukaryotic cell libraries encoding a repertoire of binding molecules (binders), wherein the methods use a site-specific nuclease for targeted cleavage of cellular DNA to enhance site-specific integration of binder genes through endogenous cellular repair mechanisms. Populations of eukaryotic cells are produced in which a repertoire of genes encoding binders are integrated into a desired locus in cellular DNA (e.g., a genomic locus) allowing expression of the encoded binding molecule, thereby creating a population of cells expressing different binders.

The invention provides a dual VEGF/PDGF antagonist comprising a VEGF antagonist linked to a PDGF antagonist. The VEGF antagonist is an antibody to a VEGF or VEGFR or is a VEGFR extracellular trap segment (i.e., a segment from the extracellular region of one or more VEGFR receptors that inhibits binding of at least one VEGFR to at least one VEGF). The PDGF antagonist is an antibody to a PDGF or PDGFR or is a PDGFR extracellular trap segment (i.e., segment from the extracellular region of one or more PDGFRs, which inhibits binding of at least one PDGFR and at least one PDGF). The dual antagonist is preferably conjugated to a half-life extending moiety, such as a HEMA-PC polymer. The dual antagonist is particularly useful for treating wet aged related macular degeneration.

The invention provides a method of producing an immune complex preparation based on a secretory immunoglobulin, which is non-human secretion derived, comprising providing an industrial scale production system, capable of producing an N-glycosylated Secretory Component, producing by such system a Secretory Component comprising at least 0.01 mol non-core fucose per mol Secretory Component, and combining said Secretory Component with at least one of IgA or IgM immunoglobulins having a native glycosylation pattern to obtain an immune complex. The invention provides an isolated recombinant Secretory Component comprising the amino acid sequence of SEQ ID 1, or a functionally active variant thereof, which has a Lewis-type N-glucosylation pattern and at least 2 mol non-core fucose per mol Secretory Component; and an immune complex preparation based on a secretory immunoglobulin, derived from sources other than human secretions, comprising a Secretory Component with a Lewis-type N-glucosylation pattern and at least 0.01 mol non-core fucose per mol Secretory Component, and at least one of IgA or IgM immunoglobulins having a native glycosylation pattern.

The invention relates to a therapeutic vaccine useful against tumors exhibiting as signature the Large T antigen (LT) of the Merkel Cell PolyomaVirus (MCPyV). Additionally, the therapeutic vaccine may be also useful for preventing tumors in healthy individuals infected with MCPyV. The therapeutic vaccine involves a type-3 secretion system (T3SS) bacterial vector able to deliver a polypeptide comprising LT epitopes to antigen presenting cells (APCs), such as a truncated form of LT. The invention also relates to a fusion protein comprising a truncated form of LT.

The present disclosure relates to methods for producing recombinant proteins, as well as compositions used in and produced by such methods. Specifically, the present disclosure relates to methods for producing high secreted yields of recombinant proteins, and the compositions provided herein include recombinant host cells that comprise polynucleotide sequences encoding proteins operably linked to at least 2 distinct secretion signals.

The invention provides virus-based expression vectors comprising immune-checkpoint inhibitor inserts for use as effective adjuvants in enhancing T-cell priming to an antigen in a host during a vaccination regimen. In particular, the compositions described herein are novel recombinant modified vaccinia Ankara (MVA) viral constructs encoding one or more peptides which, upon administration, are expressed in a multimer conformation and subsequently cleaved and secreted from the cell. Such peptides are capable of downregulating an immune checkpoint pathway, for example, by inhibiting the activation of programmed-cell death protein 1 (PD-1), programed cell death ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), or another immune checkpoint regulator, or a combination thereof. When used in concert with the administration of an antigen during a vaccination strategy, the immune checkpoint expressing MVA viral construct provides significantly improved antigen-specific CD8+ T cell expansion, increased antigenic responses, and improved vaccination efficacy.

Materials and methods for using polypeptides containing fragments and variants of endostatin to treat fibrosis are described herein.